| Autor: |
Goncin, Una, Curiel, Laura, Geyer, C. Ronald, Machtaler, Steven |
| Předmět: |
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| Zdroj: |
Molecular Imaging & Biology; Apr2023, Vol. 25 Issue 2, p283-293, 11p |
| Abstrakt: |
Purpose: Our objectives were to develop a targeted microbubble with an anti-P-selectin aptamer and assess its ability to detect bowel inflammation in two murine models of acute colitis. Procedures.: Lipid-shelled microbubbles were prepared using mechanical agitation. A rapid copper-free click chemistry approach (azide-DBCO) was used to conjugate the fluorescent anti-P-selectin aptamer (Fluor-P-Ap) to the microbubble surface. Bowel inflammation was chemically induced using 2,4,6-trinitrobenzenesulfonic acid (TNBS) in both Balb/C and interleukin-10-deficient (IL-10 KO) mice. Mouse bowels were imaged using non-linear contrast mode following an i.v. bolus of 1 × 108 microbubbles. Each mouse received a bolus of aptamer-functionalized and non-targeted microbubbles. Mouse phenotypes and the presence of P-selectin were validated using histology and immunostaining, respectively. Results: Microbubble labelling of Fluor-P-Ap was complete after 20 min at 37 ̊C. We estimate approximately 300,000 Fluor-P-Ap per microbubble and confirmed fluorescence using confocal microscopy. There was a significant increase in ultrasound molecular imaging signal from both Balb/C (p = 0.003) and IL-10 KO (p = 0.02) mice with inflamed bowels using aptamer-functionalized microbubbles in comparison to non-targeted microbubbles. There was no signal in healthy mice (p = 0.4051) using either microbubble. Conclusions: We constructed an aptamer-functionalized microbubble specific for P-selectin using a clinically relevant azide-DBCO click reaction, which could detect bowel inflammation in vivo. Aptamers have potential as a next generation targeting agent for developing cost-efficient and clinically translatable targeted microbubbles. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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